In antimicrobial therapy, a continuous battle exists between the adaptation capability of microorganisms (development of resistance) and the preparation of novel drugs.
In the case of novel drugs, the adaptation capability, i.e. the resistance usually develops within a shorter or longer period. It can be expected that the development of the resistance becomes particularly rapid when the new substance is a derivative of a drug previously used for a long time since in this case, the resistance developed to the starting compound will of course more rapidly be modified for the derivatives.
The development of the resistance can be delayed by the simultaneous administration, i.e. combination of several active compounds whereby the metabolism of the microorganisms is attacked at several points at the same time. This results that the resistance of the microorganisms to the combination hardly or long afterwards develops thus, the desired "microbicidal" (killing) effect is strengthened.
In antimicrobial therapy, nalidixic acid has been used for a long time as active ingredient. It was published that from its derivatives, norfloxacin (Belgian patent specification No. 863,429) and pefloxacin (Belgian patent specifications Nos. 870,576 and 870,917) show a highly favorable effect on gram-negative pathogens whereas their effect on gram-positive pathogens is more moderate.
Tetracycline is also a long-known antimicrobial substance. Out of its derivatives, doxycycline has a very favorable effect on gram-positive pathogens and a moderate effect on gram-negative ones.